Project Summary The ability to record electrical activity from individual neurons has transformed our understanding of the nervous system1?3. Yet, it remains challenging to conclusively relate the activity of a neuron to specific features of visual perception. The goal of relating neuronal activity to perception has been hampered, in part, by an inability to measure visual function at a cellular-resolution in humans. Recently, the laboratory of Prof. Austin Roorda has developed techniques to deliver targeted spots of light small enough to stimulate individual cones in humans4,5. The ability to probe individual sensory neurons complements single-cone stimulation studies concerned with unraveling the cone contributions to visual receptive fields in lateral geniculate nucleus6 and in excised retina7 of monkey. The proposed studies will first characterize the spectral properties of a mosaic of cones using densitometry and adaptive optics. Cone-sized spots of light will then be delivered to individual cones within the classified mosaic in order to relate their spectral properties directly to visual perception in human volunteers. The results of these studies will be used to constrain the development of a population model of retinal circuitry. This work will advance our basic understanding of the neural basis of visual perception and provide valuable information for designing future therapies to rescue function in the diseased retina. Together, these experiments offer an unprecedented opportunity to link cellular physiology, anatomy and visual perception in humans and primates. Briefly, the specific aims are: Specific aim 1. Resolve the contribution and extent of retinal lateral inhibition in color vision. This aim will precisely measure the influence of lateral interactions in the appearance of color and clarify the retinal contribution to these computations. Specific aim 2. Determine how the brain combines information from individual cones. This aim will answer how accurately predictions made from single cone studies will generalize to larger stimuli. Together these two aims will clarify how color and form are represented at the most elementary level in the visual system. The results will limit the possible circuits involved in computing color information and, subsequently, inform models of retinal processing that will be immediately translatable to researcher?s designing therapeutic strategies aimed at restoring normal visual perception in the damaged retina and to tools aimed at early detection of retinal disease.